IgE is a member of the immunoglobulin family that mediates allergic responses such as asthma, food allergies, type I hypersensitivity and the familiar sinus inflammation suffered on a widespread basis. IgE is secreted by, and expressed on the surface of B-cells or B-lymphocytes. IgE binds to B-cells (as well as to monocytes, eosinophils and platelets) through its Fc region to a low affinity IgE receptor, known as FcεRII. Upon exposure of a mammal to an allergen, B-cells bearing a surface-bound IgE antibody specific for the antigen are “activated” and developed into IgE-secreting plasma cells. The resulting allergen-specific IgE then circulates through the bloodstream and becomes bound to the surface of mast cells in tissues and basophils in the blood, through the high affinity receptor also known as FcεRI. The mast cells and basophils thereby become sensitized for the allergen. Subsequent exposure to the allergen causes a cross linking of the basophilic and mast cellular FcεRI which results in degranulation of these cells and a release of histamine, leukotrienes and platelet activating factors, eosinophil and neutrophil chemotactic factors and the cytokines IL-3, IL-4, IL-5 and GM-CSF which are responsible for clinical hypersensitivity and anaphylaxis.
Antagonists that block IgE-Receptor complex formation are useful as therapeutic agents to prevent allergic response. Several therapeutic anti-IgE antibodies have been developed. These anti-IgE antibodies block IgE from binding to the high-affinity receptor FcεRI found on basophils and mast cells, and thereby prevent the release of histamine and other anaphylactic factors resulting in the pathological condition.
Anaphylaxis has been reported to occur in patients after receiving anti-IgE antibodies, such as omalizumab (e.g., Xolair®). Anaphylaxis is an acute systemic (multi-system) and very severe type I hypersensitivity allergic reaction. It is caused by degranulation of mast cells and basophils and mediated by IgE. Through 2006, 124 of 57,269 (about 0.2%) asthma patients had anaphylaxis after omalizumab administration. While there are no reports of fatal anaphylaxis as a result of omalizumab, some cases have been serious, and potentially life-threatening. For this reason, the FDA recommends that patients receiving omalizumab be monitored in the physician's office for a period of time after omalizumab administration, and health care providers administering omalizumab should be prepared to manage anaphylaxis that can be life-threatening. Sixty percent of the cases reported (124) has been after the first two doses of omalizumab. Therefore, it is possible that the reaction is from pre-existing antibodies in patients that recognize an epitope on omalizumab, as opposed to an anti-drug reaction that develops after drug administration. As anaphylaxis is associated with antibody of the IgE isotype, there is a need to develop an assay for detecting and quantitating the amount of IgE in a patient that is specific to the therapeutic anti-IgE antibody to assess the risk of anaphylaxis preferably before such anti-IgE antibody treatment and identify high risk patients.
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